Treatment of spinal muscular atrophy by sodium butyrate

doi:10.1073/pnas.171105098

Treatment of spinal muscular atrophy by sodium butyrate

^*Department of Medical Research, China Medical College Hospital, Taichung 404, Taiwan; ^‡Institute of Molecular Biology, Academia Sinica, Taipei 115, Taiwan; and ^§Departments of Pediatrics and Clinical Laboratory, Kaohsiung Medical University, Kaohsiung 807, Taiwan

Edited by Yuet Wai Kan, University of California, San Francisco, CA, and approved June 18, 2001 (received for review March 2, 2001)

Abstract

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by degeneration of the anterior horn cells of the spinal cord, leading to muscular paralysis with muscular atrophy. No effective treatment of this disorder is presently available. Studies of the correlation between disease severity and the amount of survival motor neuron (SMN) protein have shown an inverse relationship. We report that sodium butyrate effectively increases the amount of exon 7-containing SMN protein in SMA lymphoid cell lines by changing the alternative splicing pattern of exon 7 in the SMN2 gene. In vivo, sodium butyrate treatment of SMA-like mice resulted in increased expression of SMN protein in motor neurons of the spinal cord and resulted in significant improvement of SMA clinical symptoms. Oral administration of sodium butyrate to intercrosses of heterozygous pregnant knockout-transgenic SMA-like mice decreased the birth rate of severe types of SMA-like mice, and SMA symptoms were ameliorated for all three types of SMA-like mice. These results suggest that sodium butyrate may be an effective drug for the treatment of human SMA patients.

Footnotes

↵ † To whom reprint requests should be addressed. E-mail: d6781{at}www.cmch.org.tw or hungli{at}ccvax.sinica.edu.tw.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations:

SMA,

spinal muscular atrophy;

SMN,

survival motor neuron;

RT-PCR,

reverse transcriptase–PCR